Characterization of the role of neuromedin B and gastrin-releasing peptide in the mediation of stress and anxiety-related responses

The perception of an event as being potentially harmful or stressful to the individual sets off a cascade of responses, including the activation of neurons located in the hypothalamus. Despite the extensive efforts in understanding the various neurochemical systems regulating this cascade of events, many questions remain unanswered concerning the underlying mechanisms involved. Evidence from our laboratory suggests involvement of bombesin (BB; a peptide of amphibian origin), in the mediation and/or modulation of the stress response. Two BB-like peptides have been identified in mammals, gastrin-releasing peptide (GRP) and neuromedin B (NMB). Experimental evidence acquired thus far seems to suggest the potential involvement of BB-like peptides in the mediation of the stress response as well as other related responses, such as fear and anxiety. However, very few experiments have focused on determining the specific roles of NMB and GRP in mechanisms underlying the integration of stress and/or anxiety responses. Thus, the overall objective of this thesis is to clarify the intrinsic role of each of these peptides in the hope of gaining a better understanding of the underlying mechanisms mediating stress-related responses. This extensive research project provides new evidence suggesting that both endogenous BB-like peptide systems, GRP and NMB, are significantly involved in the modulation/facilitation of stress-, anxiety- and/or fear-related behaviors. Their intrinsic roles appear to be different; whereas NMB seems to mediate both anxiety and fear, GRP seems to selectively alter more robust stress-related behaviors, such as fear. This thesis project provides important additional support for the involvement of this family of peptides in stress related responses. It also provides interesting insight into the different mechanism(s) of action that might underlie stress, anxiety and/or fear. This new evidence should help in the development of more specific, and therefore efficient, therapeutic agents in the prevention and treatment of stress-related disorders